Six-membered Carbocycles Research Articles

Enantiopure η4-(1-Sulfinyldiene)Iron(0) Tricarbonyl Complexes as Templates for Carbocycle Construction via Ring-Closing Metathesis

[reaction: see text] Enantiomerically pure 1-(1Z,3E)-sulfinyl iron(0) dienols have been elaborated to bis-olefins capable of undergoing ring-closing metathesis chemistry. Using Grubbs' ruthenium carbene catalyst, a six-membered carbocycle (with one chiral center) and seven-, eight-, and nine-membered carbocycles (with two chiral centers) have been prepared. Novel transformations include the LiClO4-promoted allylation of an alkylidene malonate and a reductive sulfur-carbon bond cleavage to convert a vinyl sulfoxide into an alkene with SmI2.

Hydroxy-Directed, SmI(2)-Induced Conversion of Carbohydrates into Carbocycles.

Polyoxygenated six-membered carbocycles were derived from carbohydrates with complete stereocontrol through hydroxy-directed coupling cyclization induced by SmI(2). For example, the cis-1,3-cyclohexanediol 3 is obtained from the D-glucopyranoside derivative 1 in excellent yield. The coupling cyclization is initiated by single-electron transfer from SmI(2) to the formyl group of the delta-hydroxy aldehyde 2 generated in an equilibrium process.

Palladium-Catalyzed, Asymmetric Hetero- and Carboannulation of Allenes Using Functionally-Substituted Aryl and Vinylic Iodides

Aryl and vinylic iodides with a nucleophilic substituent in the ortho or allylic position, respectively, react with 1,2-dienes in the presence of a palladium catalyst and a chiral bisoxazoline ligand to afford five- and six-membered ring heterocycles and carbocycles in good yields and 46−88% enantiomeric excess. The generality of this process has been demonstrated by the use of nucleophilic substituents as varied as tosylamides, alcohols, phenols, carboxylic acids, and stabilized carbanions.

One-pot synthesis of five- or six-membered carbocycles through intramolecular cycloadditions by the use of ethyl chloroformate

The Michael addition reactions of β-nitrostyrenes 1 with 4-pentene-1-magnesium bromide 2a or 3-butene-1-magnesium bromide 2b generated nitronates 3 or 4. Medium to high yields of isoxazolidine derivatives 9 and 10 were obtained when nitronates 3 or 4 were treated with ethyl chloroformate and catalytic amount of 4-dimethylaminopyridine (DMAP) at room temperature in one-pot and the ratios of trans-9: cis-9 were from 1:3.00 to 1:4.06 and the ratios of trans-10:cis-10 were >99:1. The formation of compounds 9 is proposed to proceed through intramolecular nitrile oxide-olefin cycloadditions (INOC) because compounds 14a-d, obtained from the trapping of the nitrile oxides by ethyl chloroformate, could be isolated. The mechanism of the generation of compounds 10 is proposed to proceed through intramolecular alkoxycarbonyl nitronate-olefin cycloadditions (IAOC) to form intermediates N-(ethoxycarbonyl)isoxazolidines 13 and then eliminate EtOH and CO2 (or EtOCO2H) to yield the final products.

Formation of Four- to Six-Membered Carbocycles by Tandem Brook Rearrangement-Intramolecular Michael Reaction

Formation of Four- to Six-Membered Carbocycles by Tandem Brook Rearrangement-Intramolecular Michael Reaction

Cyclization/hydrosilylation of functionalized 1,7-dienes to form substituted six-membered carbocycles

The cationic palladium complex (phen)Pd(Me)(OEt 2) +BAr 4 −[phen = 1,10-phenanthroline; Ar = 3,5-C 6H 3(CF 3) 2] catalyzed the cyclization/hydrosilylation of functionalized 1,7-dienes to form silylated cyclohexanes in good yield and with moderate to good trans-selectivity.

Organoaluminum-Promoted Cyclization of Olefinic Epoxides. A New and Stereoselective Approach to Cyclohexane Frameworks

Abstract A new, general synthetic method of six-membered carbocycles has been demonstrated, which involves the stereocontrolled cyclization of olefinic epoxides with methylaluminum bis(4-bromo-2,6-di-t-butylphenoxide) (MABR) via the epoxide rearrangement and subsequent intramolecular ene reaction with high stereoselectivity. This strategy is shown to be highly useful in the stereoselective synthesis of the basic skeleton of various terpenes.

A Highly Stereoselective One-Pot Tandem Consecutive 1,4-Addition-Intramolecular 1,3-Dipolar Cycloaddition Strategy for the Construction of Functionalized Five- and Six-Membered Carbocycles(,)(1).

Nitronates 3, possessing a suitably located olefinic moiety and arising from conjugate addition of Grignard reagent 2 to nitro olefins 1, are trapped as silyl nitronates 8 which undergo a facile intramolecular 1,3-dipolar cycloaddition. The resulting N-(silyloxy)isoxazolidines 9 are readily transformed into isoxazolines 6 and 7 upon treatment with acid, thus completing the entire sequence in one pot. While cycloaddition to the five-membered carbocycles, in general, proceeds smoothly at rt in a stereospecific manner, that to the six-membered ring is sluggish and less selective. The advantages of this strategy over the intramolecular nitrile oxide cycloaddition, namely greater stereoselectivity and adaptability to one-pot conditions, have been demonstrated. Extensive NMR investigations unravelled the stereochemistry unambiguously and underscored the inadequacy of coupling constants alone in determining the stereochemistry in cyclopentane systems. The explanation advanced to account for the selectivities, in terms of subtle differences among the putative transition state geometries, is in qualitative agreement with widely accepted assumptions pertaining to 1,3-dipolar cycloadditions.

First examples of cobalt-mediated formal Alder ene reaction of allenynes

CpCo(CO) 2 catalyzes the Alder ene reaction of allenynes 1 to afford six-membered carbocycles in a totally regioselective manner through, presumably, η 3-allyl hydride complexes mechanism.

MACROBICYCLIC D-METAL TRIS-DIOXIMATES OBTAINED BY CROSS-LINKING WITH P-BLOCK ELEMENTS. PART VI. PREPARATION, MOLECULAR STRUCTURE AND MÖSSBAUER (57FE, 119SN) PARAMETERS OF AN IRON(II) COMPLEX WITH A MACROBICYCLIC TIN-CONTAINING TRIS-NIOXIMATE LIGAND

Abstract The tin-containing clathrochelate complex of Fe(II) with cyclohexanedione-1,2-dioxime (nioxime, H2Nx), [FeNx3(SnCl3)2]2- · (Et2NH+ 2)2 · Et2NH2 + · Cl− · 2Pri OH was prepared by slowly adding diethylamine to a solution containing the macrobicyclic [FeNx3(SnCl3)2]2- anion. The structure of the complex has been determined by X-ray methods. Crystal data: monoclinic, space group P21/c, a = 10.565(2), b = 25.413(5), c = 20.198(4)Å, β=95.40(3)°, Z = 4. The iron atoms is encapsulated by the clathrochelate ligand and surrounded by a distorted trigonal antiprismatic coordination sphere comprising by six nitrogen atoms of three dioxime residues. The experimental value of the distortion angle (ca 37.5°) is close to that predicted by the Mössbauer (57Fe) parameters (ca 40°). The average Fe-N bond length of 1.923Å is somewhat greater than that in boron-containing analogues. The Sn atoms have a slightly distorted octahedral coordination, which also correspond to Mössbauer (119Sn) spectroscopic data. The six-membered carbocycles in the dioxime fragments have a half-chair conformation with both β-carbons displaced to the opposite sides of the mid-plane of the remaining atoms. All the active hydrogen atoms of the structure are involved in a hydrogen bond system. The possibilities of use of Mössbauer parameters and their temperature dependences to determine the geometry of iron(II) tris-dioximates and the sign of Δ in Mössbauer (57Fe) spectra are discussed.

Studies on the Terpenoids and Related Alicyclic Compounds. part XLIII. Stereoselective Intramolecular Cyclization of .BETA.-Alkoxycarbonyl-.OMEGA.-formylallylsilanes into Bicyclic .ALPHA.-Methylene-.GAMMA.-lactones.

α-Methylene-γ-lactones fuses to five- and six-membered carbocycles were efficiently synthesized from β-ethoxycarbonyl-ω-formylallylsilane derivatives by means of the intramolecular Hosomi reaction. The formylated allylsilanes (11a, b, 12a and b) were synthesized from ethyl β-trimethylsilylpropionate and ω-tetrahydropyranyloxy-pentanal (4a) and -hexanal (4b) in several steps. The cyclization reaction of these aldehydes was performed under mild conditions with a high degree of stereocontrol. Treatment of the (E)- and (Z)-isomers of the allysilanes (11a and 12a) with titanium tetrachloride or boron trifluoride etherate gave a five-membered cis-hydroxy ester (13a). Treatment of the (Z)-allylsilane derivative (11b) with titanium tetrachloride afforded a six-membered cis-hydroxy ester (13b) as a major product together with the trans-isomer (14b), and treatment with boron trifluoride etherate selectively gave the cis-isomer (13b). On the other hand, treatment of (E)-allylsilane (12b) with titanium tetrachloride selectively gave the cis-hydroxy ester (13b), while the use of boron trifluoride etherate exclusively afforded the trans-isomer (14b).These stereoselectivities can be explained in terms of chelated transition models. Lactonization of these hydroxy esters afforded the corresponding fused α-methylene-γ-lactones (16a, 17a and b) in good yields.

Chiral spiro-connected 2,3,3-trisubstituted oxiranes New dopants for induced ferroelectric phases

Abstract The synthesis, phase behaviour and spontaneous polarization of a new class of chiral dopants for induced ferroelectric phases of general structure A and B, possessing a 2,3,3-trisubstituted oxirane ring spiro-connected with four-, five- or six-membered carbocycles are described. In a series of these compounds with the same mesogenic building blocks the one with the five-membered carbocycle exhibits the highest induced spontaneous polarization. Introduction of a carbonyl group adjacent to the oxirane ring leads to an increased induced spontaneous polarization. The sign of the helical twisting power is positive for compounds with a cyclobutane ring and negative for those with a cyclopentane or a cyclohexane ring, although the absolute configuration at the chiral carbon is the same for all compounds.

Cyclization reactions of ?-tosyloxy-1-alkynyl- and ?-tosyloxy-1-alkenylborates and their ?-halo analogues

The reaction of trialkylboranes with ω-tosyloxy-1-lithio-1-alkynes can induce transfer of an alkyl group from the boron atom to the alkynyl carbon atom with concomitant formation of four- through six-membered carbocycles via intramolecular displacement of the ω-tosyloxy group. The stereoselectivity of the reaction, however, is low (anti/syn≃1.6–1.7). The corresponding reaction of ω-halo- or ω-tosyloxy-1-alkenylborates also gives exocyclic alkenes via 1,2-migration-cyclization followed by dehydroboration. In the cases of cyclopropanation, cyclopropylcarbinyl-to-homopropargyl rearrangement rather than dehydroboration takes place. Diphenylzirconocene reacts similarly with 6-lithio-5-hexynyl tosylate to give phenylmethylenecyclopentane in 45% yield. On the other hand, attempts to induce a similar migration with phenyl derivatives of Y, V, Cr, and Mn have led to < 5–10% yields of the same cyclization product.

A systematic study of benzyl cation initiated cyclization reactions

A systematic investigation of benzyl cation initiated cyclization reactions to form six-membered carbocycles is presented. The generation of benzyl cations from benzylic bromides, ethers, and alcohols followed by intramolecular capture provided good yields of cyclized products by use of several different cyclization terminators (e.g., phenyl, alkene, β-keto ester). A study on the effect of changing the electronic nature of substituents para to the benzyl cation showed that even electron-withdrawing substituents such as quaternary ammonium afford high yields of cyclization products. The formation of five- and seven-membered carbocycles was briefly investigated and found to be less general than the formation of the corresponding six-membered carbocycles

Automated conformational analysis from crystallographic data. 2. Symmetry-modified Jarvis–Patrick and complete-linkage clustering algorithms for three-dimensional pattern recognition

The complete-linkage and Jarvis-Patrick clustering algorithms are used to identify discrete conformational subgroups for a chemical fragment from crystal structure data. Fragment conformations are defined by Nt torsion angles for N s occurrences of the fragment in the Cambridge Structural Database. Both algorithms are extensively modified to handle 2D topological symmetry of the fragment and the 3D conformational enantiomers which occur in crystal structures. The modified procedures ensure that symmetry equivalents of a given conformation are optimally superimposed in a unique cluster. A modified single-linkage algorithm, based on cluster centroids, is used to place the discrete clusters in a single asymmetric unit of conformational space. Principal-component analysis provides a graphical representation of the clustering process. The complete-linkage and Jarvis-Patrick algorithms may be preferable to single-linkage cluster analysis [Allen, Doyle & Taylor (1991). Aeta Cryst. B47, 29-40] since they minimize the effects of 'chaining' i.e. the linkage of major clusters through a chain of outlying observations. Both of the new algorithms have been tested using a trial data set of 222 six-membered carbocycles of known conformational complexity. The new algorithms are judged to provide a more effective conformational breakdown of the trial data set (in chemical terms) than that obtained with the single-linkage method alone.

Intramolecular addition of alkyllithiums to acetylenes: Regiospecific 4-, 5-, and 6- exo-dig cyclizations

Primary acetylenic alkyllithiums bearing a phenyl substituent on the triple bond, which may be prepared in virtually quantitative yield by low-temperature lithium-iodine interchange, undergo regiospecific exo-dig cyclization via stereoselective syn-addition of CH 2Li to the carbon-carbon triple bond to give four-, five-, and six-membered carbocycles bearing an easily functionalized exocyclic lithiomethylidene moiety. Cyclization of the analogous alkyl substituted acetylenic alkyllithiums is confined to the 5- exo-dig mode.

Intramolecular hypervalent tin-oxygen interaction. The origin for fixation of six-membered carbocycles to the 1,3-diaxial conformer and for stereoselective osmylations

L'interaction diaxiale-1,3 permet une haute stereoselectivite dans l'osmylation de l'ethyleneacetal de la trimethylstannyl-5 cyclohexene-2one

Unsaturated, Branched, Six-Membered Carbocycles from 2,6-Diuloses

Abstract Mild treatment of 3,4,5-tri-O-acetyl-1,7-dibromo-1,7-dideoxyxylo-2,6-heptodiulose (2) with acetate ion in several solvents produced unsaturated, branched, six-membered carbocyclic compounds. 4S(R),5R(S),6R(S)-6-acetoxy-4-bromomethyl-4,5-epoxy-6-ethoxy-2-cyclohexenone (3) was the predominant cyclization product in ethanol solution, and the 6-methoxy analog (4) was the major product in methanol solution. Cyclization of 2, in acetone cleanly produced the cross-conjugated ketone 4S(R)-2-acetoxy-3-bromo-4-bromomethyl-4-hydroxy-2,5-cyclohexadien-1-one (5), and cyclization of the 1,7-dichloro analog of 2, compound 9, gave the corresponding dichlorocyclohexadien-1-one 11. Compound 8, the 4-O-acetyl derivative of 5, and 2,3,4,6-tetraacetoxybenzyl acetate (7) were derived from 2 in an acetic anhydride—potassium acetate mixture while the deoxycyclose D,L-(3,4,6/5)-4,5,6-tri-O-acetyl-3-C(iodomethyl)-3,4,5,6-tetrahydroxycyclohexanone (12) was the reductive cyclization product from treatment of an acetone solu...

A novel synthetic route to 3,4-benzotropolones: the expansion of a six-membered carbocycle under reducing conditions

6,7-Dimethyl-3,4-benzotropolone (III; R1= H, R2= Me) and the related 5-hydroxy-3,4-benzotropolones (III; R1= OH, R2= Me) and (III; R1= OH, R2= H) are formed in good yield when derivatives of 2-acetyl-3,4-dihydronaphthalen-1 (2H)-one ate treated with zinc in acetic acid. The reductive ring expansions are discussed in terms of cyclopropanediol intermediates.

Chemical Characterization of the Mold Product Decumbin

The molecular formula of decumbin is C16H24O4. The four oxygen atoms correspond to two free secondary hydroxyl groups and a lactone moiety. The five rings or double bonds required by the molecular formula are assigned to a strain-free α-β unsaturated lactone ring, the lactone carbonyl, a second unit which absorbs a mole of hydrogen perhaps a cyclopropane ring, and another more stable ring presumably a five or six-membered carbocycle. There is only one C-methyl group by the Kuhn-Roth procedure. Decumbin and a more recently reported compound called brefeldin A are evidently identical.